Although many studies have shown diminished performance in verbal short-term memory tasks in Alzheimer's disease, few studies have explored the neural correlates of impaired verbal short-term memory in ... [more ▼]

Although many studies have shown diminished performance in verbal short-term memory tasks in Alzheimer's disease, few studies have explored the neural correlates of impaired verbal short-term memory in Alzheimer's disease patients. In this fMRI study, we examined alterations in brain activation patterns during a verbal short-term memory recognition task, by differentiating encoding and retrieval phases. Sixteen mild Alzheimer's disease patients and 16 elderly controls were presented with lists of four words followed, after a few seconds, by a probe word. Participants had to judge whether the probe matched one of the items of the memory list. In both groups, the short-term memory task elicited a distributed fronto-parieto-temporal activation that encompassed bilateral inferior frontal, insular, supplementary motor, precentral and postcentral areas, consistent with previous studies of verbal short-term memory in young subjects. Most notably, Alzheimer's disease patients showed reduced activation in several regions during the encoding phase, including the bilateral middle frontal and the left inferior frontal gyri (associated with executive control processes) as well as the transverse temporal gyri (associated with phonological processing). During the recognition phase, we found decreased activation in the left supramarginal gyrus and the right middle frontal gyrus in Alzheimer's disease patients compared with healthy seniors, possibly related to deficits in manipulation and decision processes for phonological information. At the same time, Alzheimer's disease patients showed increased activation in several brain areas, including the left parahippocampus and hippocampus, suggesting that Alzheimer's disease patients may recruit alternative recognition mechanisms when performing a short-term memory task. Overall, our results indicate that Alzheimer's disease patients show differences in the functional networks underlying memory over short delays, mostly in brain areas known to support phonological processing or executive functioning. [less ▲]

A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during ... [more ▼]

A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor STM performance. The aim of this study was to examine the influence of semantic knowledge on verbal short-term memory storage capacity in normal aging and in AD by exploring the impact of word imageability on STM performance. Sixteen patients suffering from mild AD, 16 healthy elderly subjects and 16 young subjects performed an immediate serial recall task using word lists containing high or low imageability words. All participant groups recalled more high imageability words than low imageability words, but the effect of word imageability on verbal STM was greater in AD patients than in both the young and the elderly control groups. More precisely, AD patients showed a marked decrease in STM performance when presented with lists of low imageability words, whereas recall of high imageability words was relatively well preserved. Furthermore, AD patients displayed an abnormal proportion of phonological errors in the low imageability condition. Overall, these results indicate that the support of semantic knowledge on STM performance was impaired for lists of low imageability words in AD patients. More generally, these findings suggest that the deterioration of semantic knowledge is partly responsible for the poor verbal short-term storage capacity observed in AD. [less ▲]

The language profile of patients suffering from Alzheimer's disease (AD) is characterized not only by lexicosemantic impairments but also by phonological deficits, as shown by an increasing number of ... [more ▼]

The language profile of patients suffering from Alzheimer's disease (AD) is characterized not only by lexicosemantic impairments but also by phonological deficits, as shown by an increasing number of neuropsychological studies. This study explored the functional neural correlates underlying phonological and lexicosemantic processing in AD. Using H(215)O PET functional brain imaging, a group of mild to moderate AD patients and a group of age-matched controls were asked to repeat four types of verbal stimuli: words, wordlike nonwords (WL+), non-wordlike nonwords (WL-) and simple vowels. The comparison between the different conditions allowed us to determine brain activation preferentially associated with lexicosemantic or phonological levels of language representations. When repeating words, AD patients showed decreased activity in the left temporo-parietal and inferior frontal regions relative to controls, consistent with distorted lexicosemantic representations. Brain activity was abnormally increased in the right superior temporal area during word repetition, a region more commonly associated with perceptual-phonological processing. During repetition of WL+ and WL- nonwords, AD patients showed decreased activity in the middle part of the superior temporal gyrus, presumably associated with sublexical phonological information; at the same time, AD patients showed larger activation than controls in the inferior temporal gyrus, typically associated with lexicosemantic levels of representation. Overall, the results suggest that AD patients use altered pathways to process phonological and lexicosemantic information, possibly related to a progressive loss of specialization of phonological and lexicosemantic neural networks. [less ▲]

Personality changes are frequently described by caregivers of patients with Alzheimer's disease, while they are less often reported by the patients. This relative anosognosia of Alzheimer disease (AD ... [more ▼]

Personality changes are frequently described by caregivers of patients with Alzheimer's disease, while they are less often reported by the patients. This relative anosognosia of Alzheimer disease (AD) patients for personality changes might be related to impaired self-judgment and to decreased ability to understand their caregiver's perspective. To investigate this issue, we explored the cerebral correlates of self-assessment and perspective taking in patients with mild AD, elderly and young volunteers. All subjects assessed relevance of personality traits adjectives for self and a relative, taking either their own or their relative's perspective, during a functional imaging experiment. The comparison of subject's and relative's answers provided congruency scores used to assess self-judgment and perspective taking performance. The self-judgment "accuracy" score was diminished in AD, and when patients assessed adjectives for self-relevance, they predominantly activated bilateral intraparietal sulci (IPS). Previous studies associated IPS activation with familiarity judgment, which AD patients would use more than recollection when retrieving information to assess self-personality. When taking a third-person perspective, patients activated prefrontal regions (similarly to young volunteers), while elderly controls recruited visual associative areas (also activated by young volunteers). This suggests that mild AD patients relied more on reasoning processes than on visual imagery of autobiographical memories to take their relative's perspective. This strategy may help AD patients to cope with episodic memory impairment even if it does not prevent them from making some mind-reading errors. [less ▲]

in Journal of Clinical and Experimental Neuropsychology (2007), 29(4), 405-417

Although many studies have shown diminished performance in verbal short-term memory tasks in normal aging and Alzheimer's disease (AD), the cognitive processes responsible for this verbal short-term ... [more ▼]

Although many studies have shown diminished performance in verbal short-term memory tasks in normal aging and Alzheimer's disease (AD), the cognitive processes responsible for this verbal short-term storage (STS) impairment are still unclear for both populations. We explored verbal STS functioning in patients with AD, elderly participants, and young participants, by investigating a series of processes that could underlie STS impairments in normal elderly and AD populations. The processes we investigated were (a) the influence of lexical and sublexical language knowledge on short-term storage performance, (b) functioning of the phonological loop component via word length and phonological similarity effects, and (c) executive control processes (coordination and integration). For the AD and elderly groups, the influence of language knowledge on verbal STS performance and the functioning of the phonological loop were preserved. In contrast, the AD group showed deficits for coordination and integration processes. Our results suggest that the verbal STS deficit observed in AD patients is related to impaired executive control processes. On the other hand, language-related processes underlying passive storage capacity seem to be preserved. [less ▲]

Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral ... [more ▼]

Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex ( 6, 28, - 24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects ( 4, 22, - 22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD. Copyright (C) 2006 S. Karger AG, Basel. [less ▲]